Expression of Rictor protein in tissue of colorectal cancer and its relationships with clinicopathological features and prognosis
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摘要:目的
观察结直肠癌组织中Rictor蛋白的表达情况及其与临床病理特征、预后的关系。
方法选取接受结直肠癌根治术治疗的90例结直肠癌患者作为研究对象,收集其结直肠癌组织标本,并取对应的癌旁正常结直肠组织作为对照。采用免疫组织化学方法检测结直肠癌组织和癌旁正常结直肠组织中Rictor蛋白的表达情况,分析结直肠癌组织中Rictor蛋白表达与临床病理特征、预后的关系,并采用单因素和多因素Cox回归分析探讨结直肠癌患者预后的影响因素。
结果结直肠癌组织中Rictor蛋白阳性表达率为55.6%(50/90), 高于癌旁正常结直肠组织的11.1%(10/90), 差异有统计学意义(χ2=40.034, P < 0.001)。结直肠癌组织中Rictor蛋白阳性表达率与肿瘤最大直径、浸润深度、TNM分期、分化程度和淋巴结转移具有相关性(P < 0.05)。Rictor蛋白低表达患者的总体生存率高于Rictor蛋白高表达患者, 差异有统计学意义(P < 0.05)。Cox回归分析显示, Rictor蛋白高表达、TNM分期Ⅲ期是结直肠癌患者死亡的独立危险因素(P < 0.05)。
结论Rictor蛋白在结直肠癌组织中高表达,与肿瘤恶性生物学行为和患者预后不良有关。
Abstract:ObjectiveTo observe the expression of Rictor protein in tissue of colorectal cancer and its relationships with clinicopathological features and prognosis.
MethodsA total of 90 patients with colorectal cancer treated were collected as study objects, and colorectal cancer tissue samples were collected, and the corresponding adjacent normal colorectal tissue was selected as control. The expressions of Rictor protein in colorectal cancer tissue and adjacent normal colorectal tissue were detected by immunohistochemistry, and relationships of Rictor protein with clinicopathologic feature and prognosis were analyzed. Univariate and multivariate Cox regression analysis was used to investigate the prognostic factors of colorectal cancer patients.
ResultsThe expression rate of Rictor protein in colorectal cancer tissue was significantly higher than that in normal colorectal tissues[55.6%(50/90) versus 11.1%(10/90), χ2=40.034, P < 0.001]. The positive rate of Rictor protein in tissue of colorectal cancer was related to tumor diameter, depth of invasion, TNM stage, degree of differentiation and lymph node metastasis (P < 0.05). The overall survival rate of patients with low expression of Rictor protein was higher than that of those with high expression (P < 0.05). Cox regression analysis showed that high expression of Rictor protein and stage Ⅲ of TNM staging were independent risk factors for death of colorectal cancer (P < 0.05).
ConclusionRictor protein in colorectal cancer is highly expressed, and is associated with malignant biological behavior and poor prognosis of patients.
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表 1 不同临床病理特征患者结直肠癌组织中Rictor蛋白阳性表达情况比较[n(%)]
特征 分类 n Rictor蛋白阳性表达 χ2 P 性别 男 51 28(54.9) 0.523 0.462 女 39 22(56.4) 年龄 < 60岁 47 24(51.1) 0.682 0.402 ≥60岁 43 26(60.5) 肿瘤最大直径 < 3 cm 46 21(45.7) 6.521 0.014 ≥3 cm 44 29(65.9) 肿瘤部位 左侧结肠 28 14(50.0) 0.463 0.615 右侧结肠 31 19(61.3) 直肠 31 17(54.8) 浸润深度 T1~T2期 21 6(28.6) 11.623 < 0.001 T3~T4期 69 44(63.8) TNM分期 Ⅰ期 30 11(36.7) 9.727 < 0.001 Ⅱ期 40 24(60.0) Ⅲ期 20 15(75.0) 分化程度 低分化 23 19(82.6) 14.886 < 0.001 中分化 49 24(49.0) 高分化 18 7(38.9) 淋巴结转移 有 30 22(73.3) 8.734 < 0.001 无 60 28(46.7) 表 2 结直肠癌患者预后的单因素、多因素Cox回归分析
因素 单因素分析 多因素分析 HR 95%CI P HR 95%CI P Rictor蛋白 2.491 1.193~5.201 0.015 2.401 1.103~5.230 0.026 性别 0.894 0.491~1.635 0.718 — — — 年龄 1.174 0.626~2.202 0.618 — — — 肿瘤最大直径 2.766 1.512~5.061 0.001 0.888 0.323~2.441 0.818 肿瘤部位 0.962 0.751~1.234 0.761 — — — TNM分期 2.037 1.194~3.473 0.009 2.319 1.268~4.242 0.006 淋巴结转移 3.003 1.541~5.857 0.001 1.052 0.355~3.120 0.927 分化程度 2.001 1.426~2.811 0.001 1.939 0.839~4.478 0.121 浸润深度 2.189 1.014~4.727 0.046 1.072 0.470~2.448 0.868 -
[1] JI D B, WU A W. Organoid in colorectal cancer: progress and challenges[J]. Chin Med J, 2020, 133(16): 1971-1977. doi: 10.1097/CM9.0000000000000882
[2] 王利峰, 陈海金, 俞金龙, 等. Rictor和mTOR在结直肠癌中的表达及意义[J]. 南方医科大学学报, 2016, 36(3): 396-400. doi: 10.3969/j.issn.1673-4254.2016.03.19 [3] FENG L, XIA B, TIAN B F, et al. miR-152 influences osteoporosis through regulation of osteoblast differentiation by targeting RICTOR[J]. Pharm Biol, 2019, 57(1): 586-594. doi: 10.1080/13880209.2019.1657153
[4] 张杰, 韩增胜, 董立新, 等. miR-152和miR-448靶向于Rictor并抑制结直肠癌细胞增殖[J]. 南方医科大学学报, 2019, 39(5): 533-539. https://www.cnki.com.cn/Article/CJFDTOTAL-DYJD201905007.htm [5] DEKKER E, TANIS P J, VLEUGELS J L A, et al. Colorectal cancer[J]. Lancet, 2019, 394(10207): 1467-1480. doi: 10.1016/S0140-6736(19)32319-0
[6] JIN M, FRANKEL W L. Lymph node metastasis in colorectal cancer[J]. Surg Oncol Clin N Am, 2018, 27(2): 401-412. doi: 10.1016/j.soc.2017.11.011
[7] PARENT P, COHEN R, RASSY E, et al. A comprehensive overview of promising biomarkers in stage II colorectal cancer[J]. Cancer Treat Rev, 2020, 88: 102059. doi: 10.1016/j.ctrv.2020.102059
[8] SHAN T, CHEN S, CHEN X, et al. Association of family history of tumors with clinicopathological characteristics and prognosis of colorectal cancer[J]. Eur J Cancer Prev, 2019, 28(4): 258-267. doi: 10.1097/CEJ.0000000000000482
[9] KIM L C, RHEE C H, CHEN J. RICTOR amplification promotes NSCLC cell proliferation through formation and activation of mTORC2 at the expense of mTORC1[J]. Mol Cancer Res, 2020, 18(11): 1675-1684. doi: 10.1158/1541-7786.MCR-20-0262
[10] WONG C K, LAMBERT A W, OZTURK S, et al. Targeting RICTOR sensitizes SMAD4-negative colon cancer to irinotecan[J]. Mol Cancer Res, 2020, 18(3): 414-423. doi: 10.1158/1541-7786.MCR-19-0525
[11] PRAKASH V, CARSON B B, FEENSTRA J M, et al. Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease[J]. Nat Commun, 2019, 10(1): 2110. doi: 10.1038/s41467-019-10100-8
[12] 杨海霞, 路易玲, 黄骏. Ki-67、CARLo-5及Rictor蛋白在子宫内膜癌中的表达及预后价值[J]. 分子诊断与治疗杂志, 2021, 13(1): 123-127. https://www.cnki.com.cn/Article/CJFDTOTAL-YXYQ202101032.htm [13] WANG F, LOU X, ZOU Y, et al. Overexpression of Rictor protein and Rictor-H. pylori interaction has impact on tumor progression and prognosis in patients with gastric cancer[J]. Folia Histochem Cytobiol, 2020, 58(2): 96-107. doi: 10.5603/FHC.a2020.0015
[14] WATANABE R, MIYATA M, ONEYAMA C. Rictor promotes tumor progression of rapamycin-insensitive triple-negative breast cancer cells[J]. Biochem Biophys Res Commun, 2020, 531(4): 636-642. doi: 10.1016/j.bbrc.2020.08.012
[15] KONDO S, HIRAKAWA H, IKEGAMI T, et al. Raptor and Rictor expression in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma[J]. BMC Cancer, 2021, 21(1): 87. doi: 10.1186/s12885-021-07794-9
[16] WEN F F, LI X Y, LI Y Y, et al. Expression of Raptor and Rictor and their relationships with angiogenesis in colorectal cancer[J]. Neoplasma, 2020, 67(3): 501-508. doi: 10.4149/neo_2020_190705N597
[17] 黄仕思, 罗荣城. siRNA靶向沉默Rictor基因表达对肝癌细胞增殖、迁移和侵袭的影响[J]. 中国热带医学, 2020, 20(3): 212-218. https://www.cnki.com.cn/Article/CJFDTOTAL-RDYX202003005.htm [18] BANG H, AHN S, JI KIM E, et al. Correlation between RICTOR overexpression and amplification in advanced solid tumors[J]. Pathol Res Pract, 2020, 216(1): 152734. doi: 10.1016/j.prp.2019.152734